X Wu1, J Liu2, L G Tanadini3, D P Lammertse4, A R Blight5, John L K Kramer6, G Scivoletto7, L Jones8, S Kirshblum9, R Abel10, J Fawcett11, E Field-Fote12, J Guest12, B Levinson13, D Maier14, K Tansey15, N Weidner16, W G Tetzlaff2, T Hothorn17, A Curt18, J D Steeves2. 1. 1] ICORD, Blusson Spinal Cord Centre, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada [2] Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China. 2. ICORD, Blusson Spinal Cord Centre, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada. 3. 1] Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland [2] Epidemiology, Biostatistics and Prevention Institute, University Zurich, Zurich, Switzerland. 4. Craig Hospital, Englewood, CO, USA. 5. Acorda Therapeutics Inc. Hawthorne, NY, USA. 6. 1] ICORD, Blusson Spinal Cord Centre, Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada [2] Shepherd Center, Crawford Research Institute, Atlanta, GA, USA. 7. Spinal Unit, IRCCS Fondazione S. Lucia, Rome, Italy. 8. Craig H. Neilsen Foundation, Encino, CA, USA. 9. Kessler Institute for Rehabilitation, West Orange, NJ, USA. 10. Trauma Center Bayreuth, Bayreuth, Germany. 11. John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK. 12. Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, USA. 13. Asubio Pharmaceuticals Inc. Edison, NJ, USA. 14. Trauma Center Murnau, Murnau, Germany. 15. Departments of Neurology and Physiology, Emory University and VA Medical Center, Atlanta, GA, USA. 16. Spinal Cord Injury Center, Heidelberg University Hospital, Heidelberg, Germany. 17. Epidemiology, Biostatistics and Prevention Institute, University Zurich, Zurich, Switzerland. 18. Spinal Cord Injury Center, University Hospital Balgrist, University of Zurich, Zurich, Switzerland.
Abstract
STUDY DESIGN: This is a review article. OBJECTIVES: This study discusses the following: (1) concepts and constraints for the determination of minimal clinically important difference (MCID), (2) the contrasts between MCID and minimal detectable difference (MDD), (3) MCID within the different domains of International Classification of Functioning, disability and health, (4) the roles of clinical investigators and clinical participants in defining MCID and (5) the implementation of MCID in acute versus chronic spinal cord injury (SCI) studies. METHODS: The methods include narrative reviews of SCI outcomes, a 2-day meeting of the authors and statistical methods of analysis representing MDD. RESULTS: The data from SCI study outcomes are dependent on many elements, including the following: the level and severity of SCI, the heterogeneity within each study cohort, the therapeutic target, the nature of the therapy, any confounding influences or comorbidities, the assessment times relative to the date of injury, the outcome measurement instrument and the clinical end-point threshold used to determine a treatment effect. Even if statistically significant differences can be established, this finding does not guarantee that the experimental therapeutic provides a person living with SCI an improved capacity for functional independence and/or an increased quality of life. The MDD statistical concept describes the smallest real change in the specified outcome, beyond measurement error, and it should not be confused with the minimum threshold for demonstrating a clinical benefit or MCID. Unfortunately, MCID and MDD are not uncomplicated estimations; nevertheless, any MCID should exceed the expected MDD plus any probable spontaneous recovery. CONCLUSION: Estimation of an MCID for SCI remains elusive. In the interim, if the target of a therapeutic is the injured spinal cord, it is most desirable that any improvement in neurological status be correlated with a functional (meaningful) benefit.
STUDY DESIGN: This is a review article. OBJECTIVES: This study discusses the following: (1) concepts and constraints for the determination of minimal clinically important difference (MCID), (2) the contrasts between MCID and minimal detectable difference (MDD), (3) MCID within the different domains of International Classification of Functioning, disability and health, (4) the roles of clinical investigators and clinical participants in defining MCID and (5) the implementation of MCID in acute versus chronic spinal cord injury (SCI) studies. METHODS: The methods include narrative reviews of SCI outcomes, a 2-day meeting of the authors and statistical methods of analysis representing MDD. RESULTS: The data from SCI study outcomes are dependent on many elements, including the following: the level and severity of SCI, the heterogeneity within each study cohort, the therapeutic target, the nature of the therapy, any confounding influences or comorbidities, the assessment times relative to the date of injury, the outcome measurement instrument and the clinical end-point threshold used to determine a treatment effect. Even if statistically significant differences can be established, this finding does not guarantee that the experimental therapeutic provides a person living with SCI an improved capacity for functional independence and/or an increased quality of life. The MDD statistical concept describes the smallest real change in the specified outcome, beyond measurement error, and it should not be confused with the minimum threshold for demonstrating a clinical benefit or MCID. Unfortunately, MCID and MDD are not uncomplicated estimations; nevertheless, any MCID should exceed the expected MDD plus any probable spontaneous recovery. CONCLUSION: Estimation of an MCID for SCI remains elusive. In the interim, if the target of a therapeutic is the injured spinal cord, it is most desirable that any improvement in neurological status be correlated with a functional (meaningful) benefit.
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